An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine System
Development of tools to manipulate activity of specific neurons is important for dissecting the function of neural circuits. Viral vectors and conditional transgenic animal lines that target recombinases to specific cells facilitate the successful manipulation and recording of specific subsets of ne...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00049/full |
| _version_ | 1818309495368974336 |
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| author | Nefeli Kakava-Georgiadou Maria M. Zwartkruis Maria M. Zwartkruis Clara Bullich-Vilarrubias Clara Bullich-Vilarrubias Mieneke C. M. Luijendijk Keith M. Garner Geoffrey van der Plasse Roger A. H. Adan Roger A. H. Adan |
| author_facet | Nefeli Kakava-Georgiadou Maria M. Zwartkruis Maria M. Zwartkruis Clara Bullich-Vilarrubias Clara Bullich-Vilarrubias Mieneke C. M. Luijendijk Keith M. Garner Geoffrey van der Plasse Roger A. H. Adan Roger A. H. Adan |
| author_sort | Nefeli Kakava-Georgiadou |
| collection | DOAJ |
| description | Development of tools to manipulate activity of specific neurons is important for dissecting the function of neural circuits. Viral vectors and conditional transgenic animal lines that target recombinases to specific cells facilitate the successful manipulation and recording of specific subsets of neurons. So far, it has been possible to target neuronal subtypes within a certain brain region based on transcriptional control regions from a gene selectively expressed in those cells or based upon its projections. Nevertheless, there are only a few tools available that combine this and target a neuronal subtype within a projection. We tested a viral vector system, consisting of a canine adenovirus type 2 expressing a Cre-dependent Flp recombinase (CavFlexFlp) and an adeno-associated viral (AAV) vector expressing a Flp-dependent cDNA, which targets neurons in a subtype- and projection-specific manner. As proof of principle we targeted expression of a Designer Receptor Exclusively Activated by Designer Drugs (DREADD) to the dopamine neurons of the mesolimbic projection, which allows the transient activation of neurons by the ligand Clozapine-N-Oxide (CNO). We validated that the system specifically targets dopamine neurons and that chemogenetic activation of these neurons induces an increase in locomotor activity. We thus validated a valuable tool that allows in vivo neuronal activation in a projection- and subtype-specific manner. |
| first_indexed | 2024-12-13T07:31:04Z |
| format | Article |
| id | doaj.art-eec5557d9899403bacbfd9f1f042c672 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-13T07:31:04Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-eec5557d9899403bacbfd9f1f042c6722022-12-21T23:55:13ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-02-011210.3389/fnmol.2019.00049437589An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine SystemNefeli Kakava-Georgiadou0Maria M. Zwartkruis1Maria M. Zwartkruis2Clara Bullich-Vilarrubias3Clara Bullich-Vilarrubias4Mieneke C. M. Luijendijk5Keith M. Garner6Geoffrey van der Plasse7Roger A. H. Adan8Roger A. H. Adan9Division of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, NetherlandsDivision of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, NetherlandsMaster’s Program Neuroscience and Cognition, Utrecht University, Utrecht, NetherlandsDivision of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, NetherlandsMaster’s Program Neuroscience and Cognition, Utrecht University, Utrecht, NetherlandsDivision of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, NetherlandsDivision of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, NetherlandsDivision of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, NetherlandsDivision of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, NetherlandsInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDevelopment of tools to manipulate activity of specific neurons is important for dissecting the function of neural circuits. Viral vectors and conditional transgenic animal lines that target recombinases to specific cells facilitate the successful manipulation and recording of specific subsets of neurons. So far, it has been possible to target neuronal subtypes within a certain brain region based on transcriptional control regions from a gene selectively expressed in those cells or based upon its projections. Nevertheless, there are only a few tools available that combine this and target a neuronal subtype within a projection. We tested a viral vector system, consisting of a canine adenovirus type 2 expressing a Cre-dependent Flp recombinase (CavFlexFlp) and an adeno-associated viral (AAV) vector expressing a Flp-dependent cDNA, which targets neurons in a subtype- and projection-specific manner. As proof of principle we targeted expression of a Designer Receptor Exclusively Activated by Designer Drugs (DREADD) to the dopamine neurons of the mesolimbic projection, which allows the transient activation of neurons by the ligand Clozapine-N-Oxide (CNO). We validated that the system specifically targets dopamine neurons and that chemogenetic activation of these neurons induces an increase in locomotor activity. We thus validated a valuable tool that allows in vivo neuronal activation in a projection- and subtype-specific manner.https://www.frontiersin.org/article/10.3389/fnmol.2019.00049/fullVTAdopamineDREADDchemogeneticsCav2canine |
| spellingShingle | Nefeli Kakava-Georgiadou Maria M. Zwartkruis Maria M. Zwartkruis Clara Bullich-Vilarrubias Clara Bullich-Vilarrubias Mieneke C. M. Luijendijk Keith M. Garner Geoffrey van der Plasse Roger A. H. Adan Roger A. H. Adan An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine System Frontiers in Molecular Neuroscience VTA dopamine DREADD chemogenetics Cav2 canine |
| title | An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine System |
| title_full | An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine System |
| title_fullStr | An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine System |
| title_full_unstemmed | An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine System |
| title_short | An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the Mesolimbic Dopamine System |
| title_sort | intersectional approach to target neural circuits with cell and projection type specificity validation in the mesolimbic dopamine system |
| topic | VTA dopamine DREADD chemogenetics Cav2 canine |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00049/full |
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